FIRST PUBLISHED IN ISSUE 90 (2008)

 

 

HORSES CAN GET CUSHING’S

Cushing’s is found in humans and dogs, but it is also the most common endocrine disorder to affect middle-aged and geriatric horses. It is found so often that some believe it is part of the natural ageing process.

Equine Cushing’s syndrome is generally caused by hypertrophy, hyperplasia or adenoma formation in the pituitary gland, although it can also be caused by adrenal tumours. Horses tend to develop pituitary adenomas that originate from the pars intermedia, whereas in humans the adenoma can also originate from the pars distalis. In horses, the most obvious clinical finding is hirsutism (a long coat that fails to shed), but other clinical signs may include polydipsia, polyuria, hyperglycaemia, muscle wastage and laminitis (failure of the bond between the hoof wall and the bone in the foot). The symptoms are controlled through changes in management and/or drug therapy (most commonly with pergolide).

Metabolic syndrome can affect horses as well as humans. Human metabolic syndrome is characterised by obesity, insulin resistance, hypertension and dyslipidaemia. Peripheral Cushing’s syndrome or equine metabolic syndrome is characterised by the combination of obesity, insulin resistance and laminitis in mature horses. The effectiveness of insulin signalling at insulin-sensitive target cells is often found to be impaired in native pony breeds, particularly in obese animals, and insulin resistance is thought to be a risk factor for laminitis. It has also been suggested that chronic insulin resistance can predispose an animal to Cushing’s syndrome. There is an increasing body of evidence that suggests that certain animals may have a genetic and phenotypic predisposition to the development of equine metabolic syndrome.

LIANE CROWTHER
The Horse Trust (correct at the time of first publication)

 

GROWTH HORMONE BOOSTS COMMERCIAL MILK PRODUCTION

Growth hormone (GH), also known as bovine somatotropin (BST), is used commercially in the USA and elsewhere to increase the milk yield of dairy cows.

The increase is about 10–20%. GH is a homeostatic repartitioning agent, which means it redirects nutrients away from body tissues (adipose tissue and muscle) and towards the mammary gland, where they are synthesised into milk. It works exquisitely to increase the lifespan and synthetic capacity of the milk secretory cells, and the blood flow through the mammary gland, and to reduce the rate of uptake of nutrients at other tissues. The yield-enhancing effects of GH occur within a matter of days. Over a period of weeks, the appetite of the dairy cow is also increased; in the meantime the energy balance of the cow is reduced, such that the additional milk comes from body reserves. GH is administered commercially once every 2 weeks as a slow-release subcutaneous injection.

These effects were first identified before World War Two. Extracting GH from the pituitary glands of culled cattle was considered as a way of increasing the UK’s milk supply during the war. But the amount that could be produced in that way would have had a negligible effect on the milk supply of the country. It was the advent of recombinant DNA technology in the 1980s that led to a method of producing copious amounts of GH and enabled its commercialisation during the 1990s.

Use of GH in this way is highly controversial. Its use in the EU and elsewhere is prohibited because of possible (though unlikely) adverse health effects on human consumers of milk, and because of the real adverse health effects it has on the cows. Meta-studies of BST use have shown increased rates of mastitis and lameness in dairy cows, as well as an incidence of infections at the injection site. Even in the USA there are now increased calls for this synthetic hormone to be banned.

MICHAEL ROSE
Aberystwyth University (correct at the time of first publication)

 

SPAWNING SALMON MAY DIE FROM ‘CUSHING’S’

With Jamie Oliver on the food revolutionary path again, this time in Rotherham, you may have seen him cajoling novices into creating healthy food in front of a large audience in the town square. Pan-fried salmon was on the menu.

There is little debate that limited intake of salmon and other fish is good for you, as part of a balanced diet. But you may not be so familiar with data from 50 years ago, demonstrating the endocrine mayhem and ill health that the Pacific salmon appears to suffer during migration and spawning.

This amazing fish, the picture of health at sea, migrates hundreds of miles to spawning grounds, only then to die. Post-mortems of spawning fish show very advanced coronary artery disease, and vacuolation of striated muscle. The change in physical appearance from sea to spawning ground is striking, with the appearance of an almost ‘buffalo hump’ (excuse the cross-species analogy), whilst internally the intra-renal gland increases dramatically. It might not then be such a surprise to find very elevated cortisol levels in the spawning fish. Is the cause of demise Cushing’s syndrome? The clinical, anatomical, histological and biochemical data are rather compelling!

JOHN NEWELL-PRICE
University of Sheffield (correct at the time of first publication)

 

HYPERTHYROIDISM IS THE MOST COMMON ENDOCRINOPATHY IN CATS

Feline hyperthyroidism is both clinically and histopathologically very similar to toxic nodular goitre in humans (HTNG). While HTNG is more prevalent in females, the condition affects male and female cats equally. It results in debilitating disease in a significant percentage of middle-aged and older cats.

In both cats and humans, hyperthyroidism is caused by thyrotrophin (TSH)-independent overactivity of one or more benign hyperfunctioning adenomatous thyroid nodules. This leads to high circulating concentrations of thyroxine and tri-iodothyronine, which cause multisystemic clinical signs, including weight loss, increased appetite, tachycardia and polyphagia.

Most HTNG patients exhibit a gain-of-function TSH receptor gene mutation. Many of the receptor gene mutations are directly comparable between feline hyperthyroidism and HTNG. The most common somatic mutation detected in cats (a Met-452>Thr mutation) is analogous to the human Met-453>Thr observed in sporadic human hyperthyroidism.

ANDREW LOWE
From Watson et al. 2005, Journal of Endocrinology 186 523–537.

 

DOGS GET DIABETES TOO

It often surprises our medical colleagues to learn that veterinary surgeons diagnose and treat diabetes in companion animals in much the same way as they do in human patients. Comparative research into diabetes in dogs might offer opportunities that are not possible in rodent models.

Canine diabetes is diagnosed on the basis of clinical signs of polyuria and polydipsia, persistent hyperglycaemia and glucosuria. Virtually all diabetic dogs are insulin-deficient and are dependent upon insulin therapy. It is difficult to use the classification system for human diabetes in dogs, since the underlying cause of the beta cell loss or dysfunction is not usually investigated. However, it is clear that canine diabetes is not a single disease entity and several types of the disease occur.

Neonatal diabetes is seen in particular breeds (primarily Labradors in the UK) but is rare and seems to be due to congenital beta cell aplasia. Most diabetic dogs are diagnosed in middle age (between 5 and 12 years old). Although there is no sex predisposition, female dogs can develop diabetes during dioestrus, which is comparable with human gestational diabetes.

There are clear breed differences in susceptibility to diabetes, with Samoyeds and Tibetan and cairn terriers at an increased risk, whereas golden retrievers, German shepherd dogs and boxers are relatively resistant. This suggests that there is a genetic component to diabetes susceptibility in dogs, and recent work has implicated MHC and some other immune response genes.

There is little evidence that obesity is a major risk factor for diabetes in dogs, which is in contrast to the situation in cats. Thus, canine type 2 diabetes does not seem to exist. Since most dogs suffer from insulin deficiency, it has been suggested that the disease is most similar to the type 1 form of the disease. Although there is evidence for circulating beta cell autoantibodies (primarily against GAD65) in a proportion of diabetic dogs, most are autoantibody-negative. Furthermore, the age of onset suggests that if the beta cell loss is immune-mediated, this process might be more comparable with that seen in latent autoimmune diabetes of the adult (LADA) rather than juvenile-onset type 1A diabetes. Chronic subclinical pancreatitis is also believed to contribute to beta cell loss or dysfunction in some cases.

Much remains to be investigated in terms of the genetic and environmental factors that contribute to canine diabetes susceptibility and the mechanisms that lead to beta cell dysfunction. However, veterinarians aim to contribute to the research effort into this disease, alongside basic science and medical colleagues.

BRIAN CATCHPOLE
Royal Veterinary College, University of London (correct at the time of first publication)

 

BIRDS MAY SHOW DEVELOPMENTAL RESPONSES TO STRESS

The long term effects of developmental stress have been studied in mammalian models for many years, to understand not only the underlying mechanisms, but also to determine the consequences for human health.

These studies have shown that exposure to glucocorticoid stress hormones during development can permanently alter the reactivity of the hypothalamic-pituitary-adrenal axis. Treatment can also have significant effects on adult behaviour, cognitive ability and important indicators of diseases such as cardiovascular disease and diabetes. However, the continued physiological link between mother and offspring during development constrains the ability to determine the direct effects of stressors on subsequent physiology and behaviour.

Researchers at the University of Glasgow are now using birds to understand the role of glucocorticoid programming in shaping adult phenotypes. Here, there is only a brief window of opportunity for a mother to invest glucocorticoid hormones into each egg, and no direct maternal input of hormones during postnatal development. This therefore allows precise quantification of exposure levels and the scope for controlled experimental manipulation of glucocorticoid levels at several developmental stages.

Although currently in the early stages, this model could provide an important tool in understanding the basic mechanisms underlying the long term effects of developmental stress in humans.

KAREN SPENCER
University of Glasgow (correct at the time of first publication)